Epidemiologic studies have clearly demonstrated that patients with a preponderance of abdominal or visceral adiposity are at profoundly higher risk for cardiovascular disease than those with preferential accumulation of body fat in the gluteofemoral region. Atherogenic abnormalities associated with visceral adiposity include increases in inflammatory cardiovascular risk markers, dyslipidemia and insulin resistance. Cardiovascular disease is the leading cause of death and illness in developed countries. Therefore, the investigation of possible mechanisms underlying the increased cardiovascular risk in patients with visceral adiposity is critical, as is the development of potential therapies for this disorder. An elevated risk of visceral adiposity and cardiovascular risk has been established in men and women with growth hormone (GH) deficiency due to hypopituitarism. Studies have been fundamental in establishing that decreased GH secretion is an independent risk factor for visceral obesity and cardiovascular disease in such patients. GH administration has been shown to decrease visceral adiposity in women with GH deficiency due to hypopituitarism, but cardiovascular risk markers have not been studied, nor have men and women with GH deficiency due to obesity in the absence of pituitary disease. Our preliminary data suggest a strong association between GH deficiency, truncal adiposity and increased cardiovascular risk markers in overweight normal women without pituitary disease. This is consistent with limited published studies suggesting that GH secretion may be reduced in morbidly obese compared with lean men and women in the absence of pituitary disease. In this proposal, we will investigate, in a double-blind, randomized, placebo-controlled protocol whether low-dose GH administration improves markers of cardiovascular risk in parallel with reductions in visceral fat mass in the normal men and women with visceral adiposity and diminished GH secretion. [unreadable] [unreadable] [unreadable]